The present invention relates to filters for use in microfluidic devices and methods for their use and manufacture.
There has been a growing interest in the manufacture and use of microfluidic systems for the acquisition of chemical and biological information. In particular, when conducted in microfluidic volumes, complicated biochemical reactions may be carried out using very small volumes of liquid. Among other benefits, microfluidic systems increase the response time of reactions, minimize sample volume, and lower reagent consumption. When volatile or hazardous materials are used or generated, performing reactions in microfluidic volumes also enhances safety and reduces disposal quantities.
Traditionally, microfluidic devices have been constructed in a planar fashion using techniques that are borrowed from the silicon fabrication industry. Representative systems are described, for example, in some early work by Manz et al. (Trends in Anal. Chem. (1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66). In these publications, microfluidic devices are constructed by using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. A cover plate is bonded to the top of the device to provide closure. Miniature pumps and valves can also be constructed to be integral (e.g., within) such devices. Alternatively, separate or off-line pumping mechanisms are contemplated.
More recently, a number of methods have been developed that allow microfluidic devices to be constructed from plastic, silicone or other polymeric materials. In one such method, a negative mold is first constructed, and plastic or silicone is then poured into or over the mold. The mold can be constructed using a silicon wafer (see, e.g., Duffy et al., Analytical Chemistry (1998) 70: 4974-4984; McCormick et. al., Analytical Chemistry (1997) 69: 2626-2630), or by building a traditional injection molding cavity for plastic devices. Some molding facilities have developed techniques to construct extremely small molds. Components constructed using a LIGA technique have been developed at the Karolsruhe Nuclear Research center in Germany (see, e.g., Schomburg et al., Journal of Micromechanical Microengineering (1994) 4: 186-191), and commercialized by MicroParts (Dortmund, Germany). Jenoptik (Jena, Germany) also uses LIGA and a hot-embossing technique. Imprinting methods in PMMA have also been demonstrated (see, Martynova et al., Analytical Chemistry (1997) 69: 4783-4789) However, these techniques do not lend themselves to rapid prototyping and manufacturing flexibility. Additionally, the foregoing references teach only the preparation of planar microfluidic structures. Moreover, the tool-up costs for both of these techniques are quite high and can be cost-prohibitive.
Various conventional tools and combinations of tools are used when analyzing or synthesizing chemical or biological products in conventional macroscopic volumes. Such tools include, for example: metering devices, reactors, valves, heaters, coolers, mixers, splitters, diverters, cannulas, filters, condensers, incubators, separation devices, and catalyst devices. Attempts to perform chemical or biological synthesis in microfluidic volumes have been stifled by difficulties in making tools for synthesis at microfluidic scale and then integrating such tools into microfluidic devices. Additionally, difficulties in rapidly prototypic microfluidic devices are compounded by attempts to incorporate multiple synthesis tools for multi-step synthesis.
One particular difficulty is filtering fluids within microfluidic devices. Microfluidic devices have channels that are, by definition, very smallxe2x80x94typically having at least one dimension less than five hundred microns. A consequence of these small dimensions is the difficulty of inserting discrete elements into a microfluidic structure. For example, a typical microfluidic device may be constructed from micro-machined or etched silicon (as discussed above), polymeric stencil layers (as discussed below), or any other suitable material. One characteristic of these materials is that they are not generally porous. Thus, in order to perform a filtering function, a porous material (providing the desired filtration properties or characteristics) must be inserted into the microfluidic structure of the device at the appropriate location. Of course, because the dimensions of the microfluidic structures are so small, any such filter material to be inserted into a device may be small and fragile, making assembly processes delicate and consequently less efficient. Moreover, it has been found that filter elements inserted into, for example, a channel, are difficult to seal. As a result, some fluid tends to pass around the filter rather than through it, impairing the performance of the device.
Thus, it would be desirable to provide a filter for microfluidic devices that is easy to assemble. It is also desirable to provide a filter for microfluidic devices that seals tightly and prevents fluid from passing around, rather than through, the filter element.
In a first aspect of the invention, a multi-layer microfluidic device comprises a microfluidic inlet channel and a microfluidic outlet channel having a first height. A device layer is disposed between the inlet channel and the outlet channel. The device layer defines an aperture. A filter element having a second height is disposed in the microfluidic outlet channel below the aperture. The height of the filter is greater than the height of the outlet channel.
In another aspect of the invention, a multi-layer microfluidic device comprises a first device layer defining a microfluidic inlet channel. A second device layer defines a microfluidic outlet channel. The second device layer has a first thickness. A third device layer is disposed between the first device layer and the second device layer. The third device layer defines an aperture. A filter element is disposed substantially within the second device layer below the aperture. The filter element has a second thickness. The height of the filter is greater than the height of the second device layer.
In another aspect of the present invention, a multi-layer microfluidic device comprises a first device layer defines a first channel. A second device layer defines a second channel. A filter element is compressively fixed between the first channel and the second channel. The first channel, the second channel and the filter element are in fluid communication to define a fluid flow path. Substantially all of the fluid flow path traverses the filter element.
In another aspect of the invention, any of the foregoing aspects may be combined for additional advantage. These and other aspects of the invention are provided hereinafter.